Mast Cell Activation And Histamine Intolerance

Photo of Dr. Sharol with a big smile in oval photo frame
Drawing of mast cell.

Mast Cells

Mast cells are an immune cell in the bodies immune system. They are made in the bone marrow and present in most tissues of the body. They are found in connective tissue all through the body, especially under the skin, near blood vessels and lymph vessels, in nerves, and in the lungs and intestines. You find them in the largest amounts in tissues that are associated with the outside world. Their primary job is to coordinate how the immune system and the nervous system respond to infections and toxins.

Mast cells help control types of immune system responses and help repair tissues. They contain chemicals such as histamine, heparin, cytokines, and growth factors. They release these chemicals during certain immune responses and allergic reactions. These chemicals have many effects, including the widening of blood vessels and creation of new blood vessels. Although, they are a necessary part of body function they are also responsible for promoting inflammatory and allergic reactions.

 

Mast Cell Activation and Degranulation

This is the process of the mast cell being activated and then releaseing the chemicals that are inside of it, such as histamine, serotonin, eicosanoids such as thromboxanes, leukotrienes and prostaglandins, as well as inflammatory cytokines like TNF-alpha, chemokines and IL-4, and ATP.

Symptoms

  • Itching of the skin
  • Red bumps on the surface of the skin that itch
  • Swelling of the skin
  • Flushing or reddening of the skin
  • Hives
  • Swelling of the eyes or throat following exposure to a suspected allergen
  • Wheezing or difficulty breathing following exposure to an allergen or toxin
  • Heart palpitations, rapid pulse following a food like peanuts, dairy, wheat, corn, soy or other food
  • Low blood pressure and passing out
  • Gastrointestinal inflammation causing symptoms such as nausea, vomiting, diarrhea and cramp-like abdominal pain
  • Brain fog or disorientation following exposure to an allergen or toxin

 

How Mast Cells Are Activated

  • Masts cells can be activated by medications, foods, infections, and toxins.
  • Sometimes they go haywire and release mediators due to abnormal signals of the body.
  • Sometimes there are mast cell mutations, and they overproduce, and spontaneoulsy release mediators. These abnormal cells can grow out of control, and are very sensitive to activation. This is a condition called mastocytosis.
  • Sometimes mast cells are actiavted for no apparent reason. This is called idiopathic mast cell activation syndrome (MCAS).
  • Mast cell activation, and degranulation involves the release of mediators such as histamine, serotonin, eicosanoids such as thromboxanes, leukotrienes and prostaglandins, as well as inflammatory cytokines like TNF-alpha, chemokines, and IL-4. Additionally, mast cells will store, and release ATP into the extracellular environment. The result is an inflammatory response that can have various systemic and localized effects.
  • When there is an abundance of toxins or pathogens in the body and it overloads the body, this causes the mast cells to be overstimulated and hyperreactive. Now any stimulus, even tiny ones can cause mast cells to react and release their packets of chemicals, the main one being histamine. This kind of reaction is seen often in people with mold illness or the Lyme co-infection called Bartonella, but can also be from any type of over-burdeon of environmental toxins or pathogen toxins that are irritating and inflamming the body. We call this response "Mast Cell Activation Disorder".

Mast Cell Activation Disorder

Many symptoms, but the most common would be reacing to a food or drink within 15 minutes after eating it.  If immediately after eating or drinking something the person's skin flushes and they start to sweat, their heart races, get itchy, hives appear on the skin, they feel anxious, have abdominal pain and get diarrhea, then they should ask their Doc to consider Mast Cell Activation Disorder.

Lab Tools

Increases in serum mast cell trypatase and urinary levels of N-methylhistamine, 11B-Prostaglandin F2alpha and/or Leukotriene Ef are the tests used to diagnose MCAS.

Total serum mast cell tryptase should be drawn between 30 minutes and two hours after the start of an episode, with baseline level obtained many days later. The urine tests are performed on a 24 hour collection of urine that is started immediately.

The problem with testing for any of the chemicals released by mast cells is that they disappear extremely quickly and if you don't test while in the middle of an episode, your test will likely come up negative.

What To Do?

The best thing to do if a person has a Mast cell activation disorder is to figure out what is triggering it. Look for the toxins from the environment or pathogens. Then take care of them. This should stop the mast cell activation. In the mean time, while figuring this out and treating the issue, there are many things that can be done to make the person feel better.

Histamine And Foods

All foods considered to be high histamine should be suspect as they can add fuel to the fire going on in your body. You are reacting to histamine released by your immune system and high histamine foods will bother you if you run out of one or both enzymes that remove histamine (usually diamine oxidase or DAO). Histamine can be metabolized in 2 ways: by oxidative deamination by DAO (former name: histaminase) or by ring methylation by histamine-N-methyltransferase (HNMT). DAO is released into the circulation and  is concentrated in the small intestine where it neutralizes the histamine in food or histamine made by some gut bacteria from histidine in your food. HNMT breaks down histamine at an intracellular level. It is found in high levels in the liver, and kidney and is important at breaking down histamine in the nervous system. HNMT is also important in the airway, where it protects against histamine in these tissues, including the bronchial epithelium where it protects against histamine induced asthma. Most people make plenty of these enzymes to take care of the incoming histamine, however when mast cells are releasing a lot of histmine, there is not enough enzymes to deal with it. Besides running out of  enzymes, they may not have enough of the necessary nutrients to make the enzymes that degrade the histamine, or they might have a decreased ability to make these enzymes for genetic reasons.

There are both foods high in histamine as well as foods that compete for the same enzymes needed to degrade histamine and foods that trigger mast cell release of histamine. All these categories will add to the histamine load and inflammation in the body for people who are sensitive. Foods high in histamines include alcohol (think red wine, beer), aged meats, spoiled meat, shellfish and fermented products Then there is the fact that histamine is made from the amino acid histidine. A carboxyl group is removed from the amino acid histidine and it becomes histamine. Some bacteria and yeast can change histidine in foods to histamine, which is why fermented foods containing protein can be high in histamine. Some gut bacteria can turn histidine in foods into histamine also. This means a person with dysbiosis (gut bacteria imbalance) may end up making histamine from any high protein food containing histidine. Such foods are beef, bison, pork, parmesan cheese, pork, chicken, turkey, lamb, soy, fish such as tuna, catfish and to a lesser degree seeds, nuts and beans and even lesser degree, grains. Here is a list of foods high in histidine. Note that some cuts of meat are lower than others from the same animal.

There are also some foods that trigger histamine release from mast cells. These include fruits such as chocolate, nuts, shellfish, bananas, tomatoes, kiwi, lime, lemon, pineapple, papaya and plum. Additionally some additives such as MSG, sulfites, nitrites, benzoate and artificial food colorings can increase histamine reactions in the body.

There are some drugs known to block HNMT.

If an individual is taking one of these drugs, they may be adding to the excess histamine level in their body.

• Chloroquine (Amodiaquin, an antimalarial))

• Chloroguanil

• Folate antagonists such as metoprine (HNMT requires folate for activity)

• Hydroxychloroquine

• Pyrimethamine

• Promethazine

• Tacrine (anticholinesterase, early Alzheimer’s drug)

 

Histamine Intolerance Or Low Histamine Enzymes

For people who have been diagnosed with histamine intolerance, or mast cell activation disorder, there are all sorts of things that can support them. Here are a few ideas.

DAO with meals - Besides avoiding high histamine foods or foods that induce histamine release, some people take DAO 30 minutes before eating a meal.

Support Making Enzymes
  • Make sure the person has the nutrients for DAO, MAO and  HNMT, as well as taking DAO with meals.
  • DAO deficiency is associated with low B6 and copper deficiencies. Making sure these are adequate as necessary. Remember copper used long term needs to be taken with zinc in 1:8 (copper:zinc) proportion.
  • Bifido bacteria (helpful probiotic that does not increase histamine - take after dinner and away from anti-microbials)
Demulcent herbs to consider if there is an irritated gut from excess histamine
  • Licorice
  • Marshmallow
  • Calendula
  • Slippery elm
  • Plaintain.
Also consider gut healing nutrients
  • Glutamine
  • Zinc
  • Vitamin A
  • Acetyl-l-carnitine
  • Alpha lipoic acid
Help with gas and bloating
  • Ginger
  • Peppermint

If there are pathogens found on testing, they must first be dealt with or no amount of healing activity will give persistent relief.

 

Support  Stabalizing Mast Cells (Immune Support)
  • Fish oil to stabilize cell membranes and decrease inflammation/histamine leakage from mast cells
  • Vitamin C to also stabalize mast cells - small doses often through-out day or 30 minutes before meals.
  • Quercetin - high doses are often helpful - up to 500 mg 4 times per day. Starting slowly moving up to this dose over a couple weeks. Some people may react to it and need super low doses (Neuroprotek LP - 40 mg) which will work for them. Take 30 minutes before meals and one before bed.
  • Phosphatidylcholine to support cell wall membranes
  • A study found mung bean sprouts (48 hours of sprout growth) provided significant protection against mast cell degranulation and histamine release due to their high flavonoid content. - 30 minutes before meals.
  • There are many herbs that stabalize mast cells and keep histamine from being released.
  • Creatine if methylation is not up to par as HNMT won’t work well with decreased methylation (most of your methylation activity goes to produce phosphatidylcholine and creatine, so supplementation helps decrease need for methylation if that is an issue for the individual)
  • Perimine (extract of Perilla seed) - One capsule 30 minutes before meals.
  • AllQlear - Made from quail eggs. Contains a tryptase blocker - tyrptase is another mediator released from Mast cells. 1-2 tablets 30 minutes before meals.

There are many herbs that stabalize mast cells and keep histamine from being released.

Polyphenols And Mast cell Stabilization

Foods high in a class of polyphenols called flavonoids are able to assist in decreasing mast cell activation and reduce histamine in the body.  These flavonoids include quercetin and catechin which are found in herbs such as Green tea, Chamomile, Hawthorne and Gingko. Quercetin is found in many foods/herbs and some good choices for quercetin content are garlic, onions, capers, fruits with dark red or blue colors such as blueberries and cranberries.  Elderberries are high in quercetin as well as Lovage and kale. Quercetin’s anti-inflammatory activity appears to be due to its antioxidant effects and inhibition of cyclooxygenase and lipoxygenase, which in turn regulate the inflammatory mediators leukotrienes and prostaglandins. Quercetin has been shown to stabilize mast cells, which inhibits release of histamine.

 

Research Studies Identified  Herbal Constituents That  Stabilize Mast Cells
  • Epigallocatechin gallate found in Green tea – Camellia sinensis can inhibit the release of histamine from mast cells.
  • Theanine is another constituents found in Green tea - Camellia sinensis. This amino acid has been shown to prevent histamine release from cells when in low concentrations.
  • Ellagic acid found in fruits such as raspberries, strawberries, walnuts and pomegranate  inhibit histamine release as well as proinflammatory cytokines such as TNF-alpha and Il-6.
  • Khellin from the herb Khella – Ammi visnaga has been shown to stabilize mast cells. This is also an herb that is used to prevent Asthma attacks. I have found it especially useful in the past for exercise induced asthma. Khella is not an herb that is used for immediate relief, and high doses may cause side effects such as liver damage.)
  • Silibinin from the herb Milk thistle- Silybum marianum prevents histamine release as well as preventing release of other inflammatory cytokines from mast cells.
  • Reservatrol found in the herb Japanese knoteweed - Polygonum cuspidatum, as well as the foods grapes, peanuts, and blueberries, was found to suppress inflammatory cytokines linked to mast cell disorders, specifically tumor necrosis factor and interleukins.
  • Curcumin from the herb Turmeric – Curcuma longa prevents release of histamine by stabilizing mast cells and inhibits  cytokines IL-4 and TNF-alpha.
  • Parthenolide from the herb Feverfew – Tanacetum parthenium stabalizeds mast cells.
  • Indoline from  the herb Woad - Isatis tinctoria stabilized mast cells.
  • Estragole from the herb Basil - Ocimum basilicum reduces inflammation due to edema and arachidonic acid.

 

Additional foods/herbs that might be useful to stabilize mast cells or decrease histamine release
  • Thyme
  • Watercress
  • Pea sprouts
  • Onions
  • Garlic
  • Black cumin
  • Peppermint
  • Chamomile
  • Tarragon
  • Nettle
  • Ginger
  • Turmeric
  • Apples
  • Pomegranate
  • Peaches
  • Quince

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